Skin Accumulation Research Articles

Why Black Flowers? An Extreme Environment and Molecular Perspective of Black Color Accumulation in the Ornamental and Food Crops.

Pollinators are attracted to vibrant flower colors. That is why flower color is the key agent to allow successful fruit set in food or ornamental crops. However, black flower color is the least attractive to pollinators, although a number of plant species produce black flowers. Cyanidin-based anthocyanins are thought to be the key agents to induce black color in the ornamental and fruit crops. R2R3-MYB transcription factors (TFs) play key roles for the tissue-specific accumulation of anthocyanin. MYB1 and MYB11 are the key TFs regulating the expression of anthocyanin biosynthesis genes for black color accumulation. Post-transcriptional silencing of flavone synthase II (FNS) gene is the technological method to stimulate the accumulation of cyanidin-based anthocyanins in black cultivars. Type 1 promoter of DvIVS takes the advantage of FNS silencing to produce large amounts of black anthocyanins. Exogenous ethylene application triggers anthocyanin accumulation in the fruit skin at ripening. Environment cues have been the pivotal regulators to allow differential accumulation of anthocyanins to regulate black color. Heat stress is one of the most important environmental stimulus that regulates concentration gradient of anthocyanins in various plant parts, thereby affecting the color pattern of flowers. Stability of black anthocyanins in the extreme environments can save the damage, especially in fruits, caused by abiotic stress. White flowers without anthocyanin face more damages from abiotic stress than dark color flowers. The intensity and pattern of flower color accumulation determine the overall fruit set, thereby controlling crop yield and human food needs. This review paper presents comprehensive knowledge of black flower regulation as affected by high temperature stress, and the molecular regulators of anthocyanin for black color in ornamental and food crops. It also discusses the black color-pollination interaction pattern affected by heat stress for food and ornamental crops.

Genome-wide association analysis reveal the genetic reasons affect melanin spot accumulation in beak skin of ducks

BackgroundSkin pigmentation is a broadly appearing phenomenon of most animals and humans in nature. Here we used a bird model to investigate why melanin spot deposits on the skin.ResultsOur result showed that growth age and the sunlight might induce melanin deposition in bird beak skin which was determined by genetic factors. GWAS helped us to identify two major loci affecting melanin deposition, located on chromosomes 13 and 25, respectively. The fine mapping works narrowed the candidate regions to 0.98 Mb and 1.0 Mb on chromosomes 13 and 25. The MITF and POU2F3 may be the causative genes and synergistically affect melanin deposition during duck beak skin. Furthermore, our data strongly demonstrated that the pathway of melanin metabolism contributes to melanin deposition on the skin.ConclusionsWe demonstrated that age and sunlight induce melanin deposition in bird beak skin, while heredity is fundamental. The MITF and POU2F3 likely played a synergistic effect on the regulation of melanin synthesis, and their mutations contribute to phenotypic differences in beak melanin deposition among individuals. It is pointed out that melanin deposition in the skin is related to the pathway of melanin metabolism, which provided insights into the molecular regulatory mechanisms and the genetic improvement of the melanin deposition in duck beak.

Inhibitory effect of α-cubebenoate on atopic dermatitis-like symptoms by regulating Th2/Th1/Th17 balance in vivo

Ethnopharmacological relevanceBakumijiogan (Kampo herbal formulation) and Kangqian decoction (Chinese herbal medicine formulation) have been used for the treatment of atopic dermatitis (AD) like symptoms. Schisandra chinensis Baill (Family: Magnoliaceae) is a component of both formulations. Its extracts showed inhibition of AD. Aim of the studyWe aimed to elucidate an active phytochemical from Schisandra chinensis and evaluated its effects on AD-like symptoms. Materials and methodsWe fractionated a component from Schisandra chinensis by chasing inhibitory activity on mast cell degranulation. We identified α-cubebenoate as an active phytochemical and investigated its effects by using an in vivo 1-chloro-2,4-dinitrobenzene (CDNB)-induced AD model in BALB/c mice. Resultsα-Cubebenoate significantly decreased CDNB-induced skin hypertrophy and accumulation of mast cells in the epidermis and dermis. Increases in pro-inflammatory chemokine and cytokine levels in the skin, lymph node size, and immunoglobulin E levels in the serum were significantly ameliorated by α-cubebenoate. Conclusionα-Cubebenoate regulates dermal immune responses by suppressing the Th2/Th17/Th1 immune balances, resulting in amelioration of AD-like symptoms and suppression of immune response in lymph nodes. Thereby, this study provides evidence for its therapeutic efficacy in the treatment of AD symptoms.

Pigmentation and Flavonoid Metabolite Diversity in Immature 'Fuji' Apple Fruits in Response to Lights and Methyl Jasmonate.

Artificial pigmentation of apple fruits has been intensely evaluated to generate less pigmented red apples, which are profitable because of the changes in fruit quality. In this study, we analyzed the diversity of flavonoids and the patterns of flavonoid metabolic gene expression under light irradiation with or without methyl jasmonate (MeJA) treatment in immature (S1) and color-turning (S2) staged ‘Fuji’ apples. Further, we assessed the metabolic regulation at the gene level between anthocyanin and flavonol in light-responsive apple skins. UV-B exposure within 3 days was found to significantly stimulate anthocyanin accumulation in apple skin compared to other light exposure. S1 skin was more sensitive to UV-B and MeJA treatment, in the aspect of indaein accumulation. The enhancement of apple pigmentation following treatment with adequate levels of UV-B and MeJA was maximized at approximately 72 h. Red (range from 4.25 to 17.96 µg·g−1 DW), blue (range from 4.59 to 9.17 µg·g−1 DW) and UV-A (range from 3.98 to 19.12 µg·g−1 DW) lights contributed to the induction of idaein content. Most genes related to the flavonoid pathways increased their expression under UV-B exposure, including the gene expression of the transcription factor, MdMYB10, a well-known upstream factor of flavonoid biosynthesis in apples. The boosted upregulation of MdMYB10, MdCHS, MdF3H MdLDOX, and MdUFGT genes due to MeJA in UV-B was found and may contribute the increase of idaein. UV-A and UV-B caused higher quercetin glycoside content in both S1 and S2 apple skins than longer wavelengths, resulting in significant increases in quercetin-3-O-galactoside and quercetin-3-O-glucoside. These results suggest that the application of adequate UV-B with MeJA in less-pigmented postharvest apples will improve apple color quality within a short period.

Clinical Characteristics, Management and Triggers of Mastocytosis in a Cohort of 39 Patients

Mastocytosis is a heterogeneous group of rare disorders involving mast cell accumulation in skin and/or other organs. Mast cell disorders are classified into cutaneous (CM) and systemic forms (SM) and mast cell activation syndrome (MCAS). Little data exist on the clinical presentation and management of mastocytosis. We aimed to evaluate the clinical characteristics, triggers, and management of mastocytosis.

Effect of a Topical Collagen Tripeptide on Antiaging and Inhibition of Glycation of the Skin: A Pilot Study.

The glycation process has been recognized as one of the critical parameters that accelerate signs of skin aging, especially in skin exposed to environment factors, such as ultraviolet radiation. Although previous studies showed the anti-inflammatory and antiaging properties of the hydrolyzed collagen tripeptide (CTP), its exact mechanism is not fully understood. Therefore, in this study, we sought to investigate the effect of a topical CTP on facial skin. Our group designed a 4 week prospective, single-arm study of 22 Asian women who applied topical CTP. We observed significant improvements in skin wrinkles, elasticity, and density with a reduction in skin accumulation of advanced glycated end products (AGEs) at week 4 without any adverse effects. The in vitro study revealed a preventive effect of the topical CTP on the accumulation of AGEs, denatured collagen production, and reactive oxygen species in dermal fibroblasts. Moreover, treatment with the CTP decreased induction of matrix metalloproteinases while increasing the collagen 1 level. These results suggest that the application of a topical CTP might improve clinical aging phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.

Grafting with rootstocks promotes phenolic compound accumulation in grape berry skin during development based on integrative multi-omics analysis.

In viticulture, grafting has been practiced widely and influences grape development as well as berry and wine quality. However, there is limited understanding of the effects of rootstocks on grape phenolic compounds, which are located primarily in the berry skin and contribute to certain sensory attributes of wine. In this study, scion–rootstock interactions were investigated at the green-berry stage and the veraison stage when grapevines were hetero-grafted with three commonly used rootstock genotypes (5BB, 101-14MG, and SO4). Physiological investigations showed that hetero-grafts, especially CS/5BB, contained higher concentrations of total proanthocyanidins (PAs) and various PA components in berry skins compared with the auto-grafted grapevines. Further metabolomics analysis identified 105 differentially accumulated flavonoid compounds, the majority of which, including anthocyanins, PAs, and flavonols, were significantly increased in the berry skins of hetero-grafted grapevines compared with auto-grafted controls. In addition, transcriptomic analysis of the same samples identified several thousand differentially expressed genes between hetero-grafted and auto-grafted vines. The three rootstocks not only increased the transcript levels of stilbene, anthocyanin, PA, and flavonol synthesis genes but also affected the expression of numerous transcription factor genes. Taken together, our results suggest that hetero-grafting can promote phenolic compound accumulation in grape berry skin during development. These findings provide new insights for improving the application value of grafting by enhancing the accumulation of nutritious phenolic components in grape.

A comparative study of liposomes and chitosomes for topical quercetin antioxidant therapy

The flavonoid quercetin shows excellent antioxidant and anti-inflammatory properties and it is proposed for the prevention and treatment of various skin conditions such as melanoma. However, its low solubility and instability hinders its formulation. Therefore, the objective of the present study was to develop, characterize and compare lipidic nanoformulations of quercetin intended for dermal use. We prepared liposomes (F1, F2) and chitosomes (F3, F4) with egg phosphatidylcholine and two different concentrations of surfactant (Tween 20), using the hydration method followed by sonication and extrusion. The percentage of encapsulated quercetin (HPLC), particle size and zeta potential, the release profile of quercetin, the antioxidant action, stability and skin accumulation were evaluated. The size of the prepared vesicles was between 184 nm and 342.7 nm with a zeta potential that was negative for liposomes and positive for chitosomes. The percentage of encapsulation was over 78% for both vesicles. The quercetin encapsulated in the vesicles maintained its antioxidant activity, which was superior for chitosomes due to the synergistic action of chitosan. The release profiles showed the controlled release of quercetin. The formulations developed have the appropriate characteristics for the administration of quercetin by the dermal route.

Formulation and In vitro Percutaneous Permeation and Skin accumulation of Voriconazole Microemulsified Hydrogel

The aim of the present study was to prepare and evaluate voriconazole microemulsified hydrogel. The voriconazole microemulsified is prepared by Water Titration Method. In which voriconazole microemulsified incorporated with hydrogel, Blank gels of different polymers were prepared by distilled water. Finally, the carbopol gel was prepared by dispersing 0.5% carbopol w/v and 0.5% aloe vera powder in 100 ml of water with stirring on mechanical stir. Additionally, for preservation of formulations 0.8% methyl paraben was mixed. Oil phase was selected by dissolving the voriconazole pure in different oils, oleic acid, castor oil, coconut oil, olive oil, cooten seed mineral oil and soya oil. Oleic acid was selected on the basis of higher solubility of voriconazole in it. Combination of surfactant and co-surfactant was selected on clear visual observation. Span - 40: propylene glycol in ratio 1:1 and 2:1 selected for further preparation of microemulsion. From the study F-8, F-9, F-10, F-14 and F-15 were selected for further studies. Though F-16, F-17, F-18, F-19 and F-20 formulations are also stable, but rejected due to high concentration of surfactant can cause skin irritation, skin burning and/or other complications. Characterization of selected voriconazole microemulsion formulations were evaluated under various parameters like Droplet size, Zeta potential, Poly Dispersity Index (PDI) and (%) Drug content all results showed.

The Effect of Foliar Application of K2SO4 or KH2PO4 on Skin Color of the ‘Kyoho’ Grape

Anthocyanins in red grape skin have a positive effect on fruit color and human health. The effect of foliar potassium application on anthocyanin accumulation in grape skin is not well understood. The study aimed to better understand the mechanism of anthocyanin accumulation in grape skin in response to foliar sprays of K2SO4 and KH2PO4. In this study, we investigated the effects of foliar application of KH2PO4 (T2), K2SO4 (T1) and distilled water (CK) on the skin color of ‘Kyoho’ grapes at mid-ripe and mature stages. At 90 and 110 days after full bloom (DAFB), T2 had the greatest total soluble solids (TSS), flavonoid and total anthocyanin contents, followed by T1 and CK. At two stages, the titratable acid content decreased and the juice pH increased under T2 treatment relative to CK. T1 and T2 had lower lightness (L*) than CK, and the color index of red grapes (CIRG) under T1 and T2 increased at two stages compared to CK. KEGG metabolic pathway analysis revealed that flavonoid biosynthesis was the most significantly enriched pathway in CK vs. T2 at 90 and 110 DAFB. At 90 DAFB, T2 had higher expressions of phenylalanine ammonia-lyas (PAL), cytochrome P450 CYP73A100 (CYP73A), 4-coumarate: CoA ligase (4CL), chalcone synthase (CHS), flavanone 3-dioxygenase-like (F3H) and UDP glucose: flavonoid 3-o-glucosyl transferase (UFGT) than CK and T1. Foliar application of potassium fertilizer may accelerate anthocyanin accumulation by altering the transcript levels of PAL, CYP73A, 4CL, CHS, F3H, and UFGT of the flavonoid biosynthesis.

Permeability of Ibuprofen in the Form of Free Acid and Salts of L-Valine Alkyl Esters from a Hydrogel Formulation through Strat-M™ Membrane and Human Skin.

This paper aimed to evaluate the effect of vehicle and chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen [IBU]. In vitro permeation experiments were performed using human abdominal skin and Strat-M™ membrane. The HPLC method was used for quantitative determinations. The formulations tested were hydrogels containing IBU and its derivatives and commercial gel with ibuprofen. The results obtained indicate that Celugel® had an enhancing effect on the skin penetration of IBU. The average cumulative mass of [IBU] after 24 h permeation test from Celugel® formulation through human skin was over 3 times higher than for the commercial product. Three ibuprofen derivatives containing [ValOiPr][IBU], [ValOPr][IBU], and [ValOBu][IBU] cation were evaluated as chemical penetration enhancers. The cumulative mass after 24 h of penetration was 790.526 ± 41.426, 682.201 ± 29.910, and 684.538 ± 5.599 μg IBU cm−2, respectively, compared to the formulation containing unmodified IBU-429.672 ± 60.151 μg IBU cm−2. This study demonstrates the perspective of the transdermal hydrogel vehicle in conjunction with the modification of the drug as a potential faster drug delivery system.

The PyPIF5-PymiR156a-PySPL9-PyMYB114/MYB10 module regulates light-induced anthocyanin biosynthesis in red pear

Some cultivars of pear (Pyrus L.) show attractive red fruit skin due to anthocyanin accumulation. This pigmentation can be affected by environmental conditions, especially light. To explore the light-induced regulation network for anthocyanin biosynthesis and fruit coloration in pear, small RNA libraries and mRNA libraries from fruit skins of ‘Yunhongyihao’ pear were constructed to compare the difference between bagging and debagging treatments. Analysis of RNA-seq of fruit skins with limited light (bagged) and exposed to light (debagged), showed that PyPIF5 was down-regulated after bag removal. PymiR156a was also differentially expressed between bagged and debagged fruit skins. We found that PyPIF5 negatively regulated PymiR156a expression in bagged fruits by directly binding to the G-box motif in its promoter. In addition, PymiR156a overexpression promoted anthocyanin accumulation in both pear skin and apple calli. We confirmed that PymiR156a mediated the cleavage of PySPL9, and that the target PySPL9 protein could form heterodimers with two key anthocyanin regulators (PyMYB114/PyMYB10). We proposed a new module of PyPIF5-PymiR156a-PySPL9-PyMYB114/MYB10. When the bagged fruits were re-exposed to light, PyPIF5 was down-regulated and its inhibitory effect on PymiR156a was weakened, which leads to degradation of the target PySPL, thus eliminating the blocking effect of PySPL on the formation of the regulatory MYB complexes. Ultimately, this promotes anthocyanin biosynthesis in pear skin.

Ethylene Induced by Sound Stimulation Enhances Anthocyanin Accumulation in Grape Berry Skin through Direct Upregulation of UDP-Glucose: Flavonoid 3-O-Glucosyltransferase.

Global warming has resulted in the loss of anthocyanin accumulation in berry skin. Sound stimulation can be used as a potential method for enhancing fruit color development since many plants recognize sound vibration as an external stimulus and alter their physiological status in response to it. Sound stimulation (sine wave sound at 1000 Hz) enhanced anthocyanin accumulation in grape cultured cells and berry skins in field-grown grapevines at the early stage of ripening. The transcription of UFGT and ACO2, which encode the key enzymes in anthocyanin and ethylene biosynthesis, respectively, was upregulated in grape cultured cells exposed to sound stimulation. In contrast, the transcription of MybA1 and NCED1, which encode a transcription factor for UFGT and a key enzyme in abscisic acid biosynthesis, respectively, was not affected by the sound stimulation. A treatment with an ethylene biosynthesis inhibitor, aminoethoxyvinyl glycine hydrochloride, revered the enhancement of anthocyanin accumulation by sound stimulation. As the promoter assay using a GUS reporter gene demonstrated that UFGT promoter was directly activated by the ethylene-releasing compound ethephon, which enhanced anthocyanin accumulation in grape cultured cells, we conclude that sound stimulation enhanced anthocyanin accumulation through the direct upregulation of UFGT by ethylene biosynthesis. Our findings suggest that sound stimulation contributes to alleviating poor coloration in berry skin as a novel and innovative practical technique in viticulture.

Utilization of Sweet Potato as Pigment Source in Siamese Fighting Fish (Betta splendens) Feed

This study investigated the effect of different sweet potato varieties as dietary pigment sources on the coloration of Siamese Fighting Fish (Betta splendens). The experiment was conducted as a completely randomized design (CRD) with four treatments and three replicates. The experimental feed consisted of; control feed, 5 % orange sweet potato (OrSP), 5 % yellow sweet potato (YeSP) and 5 % purple sweet potato (PuSP). The experimental feeds were formulated with 31.18-32.01 % crude protein, 6.73 - 7.04 % crude fat and total carotenoids in control, OrSP, YeSP and PuSP were 15.63, 42.61, 38.79 and 32.32 mg/kg, respectively. Two-month male fishes were obtained from a reliable commercial farm and acclimated to the rearing environment. After the 8 weeks rearing period, the results showed that the final average weight, final average length, average daily gain, weight gain, specific growth rate and feed conversion ratio (FCR) were not significantly different between treatment groups (p > 0.05). However, dietary supplementation with sweet potato affected the color expression and carotenoid accumulation by Betta splendens. The lightness(L*) of fish fed with the control feed showed the highest value (p ≤ 0.05). The redness (a*) of fish fed with 5 % OrSP and 5 % YeSP was higher than in the other treatments (p ≤ 0.05) and the yellowness (b*) of fish fed with 5 % OrSP showed higher values than in the other groups (p ≤ 0.05). The results of carotenoid accumulation in each organ increased in all treatment groups. After 8 weeks, the fish fed with 5% OrSP showed the highest carotenoid accumulation in skin and scale, dorsal fin, anal fin and caudal fin as compared to the other groups (p ≤ 0.05).

Tanshinone IIA alleviates vitiligo by suppressing AKT mediated CD8+ T cells activation in a mouse model.

Tanshinone IIA has been reported to exhibit anti-inflammatory effects, while it is not clear whether Tanshinone IIA has protective role in vitiligo. Premelanosome (PMEL) CD8+ T cells were adoptive transferred into Krt14- Kitl* mice with Kit ligand (KITL) over-expressed, to construct the vitiligo model. Pdk1fl/fl and Stat3fl/fl mice were crossed with Cd8cre mice to establish Pdk1TKO and Stat3TKO mice. Tanshinone IIA (200 μg) was intravenous injected to treat vitiligo in mice every 3 days. The accumulation of macrophages and CD8+ T cells in the ear skin was assayed by flow cytometry. Bone marrow-derived macrophages (BMDMs) were induced and stimulated with lipopolysaccharides (LPS) and IL-4. It was found that Tanshinone IIA alleviated the development of vitiligo, impaired PMEL CD8+ T cells accumulation in the ear skin, and inhibited LPS-induced TNF-α, IL-6, and IL-1β expression and secretion in BMDMs, which could also inhibit IL-4-induced Arg-1 and Mrc-1 expression in BMDMs. In addition, Tanshinone IIA could inhibit the proliferation and cytotoxic function of CD8+ T cells indicated by the expression of Perforin, Granzymeb, and IFN-γ. Furthermore, Tanshinone IIA treated Pdk1TKO mice, not Stat3TKO mice, showed impaired PMEL CD8+ T cells accumulation in the ear skin. In summary, Tanshinone IIA alleviates vitiligo development with impaired CD8+ T cells accumulation and activation of Pdk1-Akt pathway.

Characterizing Cutaneous Drug Delivery Using Open-Flow Microperfusion and Mass Spectrometry Imaging.

Traditionally, cutaneous drug delivery is studied by skin accumulation or skin permeation, while alternative techniques may enable the interactions between the drug and the skin to be studied in more detail. Time-resolved skin profiling for pharmacokinetic monitoring of two Janus Kinase (JAK) inhibitors, tofacitinib and LEO 37319A, was performed using dermal open-flow microperfusion (dOFM) for sampling of perfusate in an ex vivo and in vivo setup in pig skin. Additionally, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) was performed to investigate depth-resolved skin distributions at defined time points ex vivo in human skin. By dOFM, higher skin concentrations were observed for tofacitinib compared to LEO 37319A, which was supported by the lower molecular weight, higher solubility, lipophilicity, and degree of protein binding. Using MALDI-MSI, the two compounds were observed to show different skin distributions, which was interpreted to be caused by the difference in the ability of the two molecules to interact with the skin compartments. In conclusion, the techniques assessed time- and depth-resolved skin concentrations and were able to show differences in the pharmacokinetic profiles of two JAK inhibitors. Thus, evidence shows that the two techniques can be used as complementary methods to support decision making in drug development.

Topical Delivery of Nanosized Hydroxycitric Acid Enriched Extract-Loaded Ethosomes for Suppression of Lipid Droplet Deposition.

The aim of this study was to improve the skin accumulation of hydroxycitric acid by using ethosomes with nanosize. We fabricated nanosized ethosome for the topical delivery of hydrophilic hydroxycitric acid and evaluated their physical properties and furthermore cytotoxicity. As results, in cell-based experiments, the use of ethosomes encapsulating hydroxycitric acid extract reduced the lipid droplet deposition in differentiated adipocytes, which was visualized by Oil Red O staining assay and also quantitatively measured by a triglyceride assay. The observed reduction in lipid droplet deposition occurred in a hydroxycitric acid extract concentration-dependent manner. In addition, the high accumulation of hydroxycitric acid in murine skin (66.28%) was observed following treatment with hydroxycitric acid extract-loaded ethosomes compared with treatment with hydroxycitric acid alone (1.19%) without ethosome as a nanocarrier. Based on these results, our findings showed that nanosized ethosomes improved the topical delivery of hydroxycitric acid and thus reduced lipid droplet deposition in adipocytes.

The Effect of Cream and Gel Vehicles on the Percutaneous Absorption and Skin Retention of a New Eugenol Derivative With Antioxidant Activity.

The effect of cream and gel vehicles containing clove water on skin permeability was compared for a new eugenol derivative (eugenyl dichloroacetate—EDChA) with antioxidant activity. In vitro permeation experiments were conducted in a Franz cell with porcine skin. The cumulative mass and skin accumulation of EDChA were investigated and compared. The antioxidative capacity of the studied vehicles was determined by using the diphenylpicrylhydrazyl (DPPH) free radical reduction method. The antioxidant activity (evaluated with DPPH, ABTS, and the Folin–Ciocalteu methods) of the fluid that penetrated through the pig skin and of the fluid obtained after the skin extraction, were also determined. For comparison, eugenol was also tested. The results of this work could contribute to the development of vehicles with antioxidant potential estimated after 24 h of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The waste water from the clove buds steam distillation -contains several valuable biologically active compounds, and its use is environmentally friendly. We observed that gel vehicles were the best enhancer of skin permeation for both eugenol and its derivative. In most cases, -similar cumulative masses of eugenol and its ester were found in the acceptor fluid. The accumulation of EDChA was higher for cream vehicles in relation to the parent eugenol when applied onto the skin. The greatest amounts of eugenol were accumulated in the skin when these compounds were used in gel vehicles.

Transdermal Delivery Systems for Ibuprofen and Ibuprofen Modified with Amino Acids Alkyl Esters Based on Bacterial Cellulose.

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.

Enhancement of the Antioxidant and Skin Permeation Properties of Betulin and Its Derivatives.

This study investigated the antioxidant activity DPPH, ABTS, and Folin–Ciocalteu methods of betulin (compound 1) and its derivatives (compounds 2–11). Skin permeability and accumulation associated with compounds 1 and 8 were also examined. Identification of the obtained products (compound 2–11) and betulin isolated from plant material was based on the analysis of 1H- NMR and 13C-NMR spectra. The partition coefficient was calculated to determine the lipophilicity of all compounds. In the next stage, the penetration through pig skin and its accumulation in the skin were evaluated of ethanol vehicles containing compound 8 (at a concentration of 0.226 mmol/dm3), which was characterized by the highest antioxidant activity. For comparison, penetration studies of betulin itself were also carried out. Poor solubility and the bioavailability of pure compounds are major constraints in combination therapy. However, we observed that the ethanol vehicle was an enhancer of skin permeation for both the initial betulin and compound 8. The betulin 8 derivative showed increased permeability through biological membranes compared to the parent betulin. The paper presents the transformation of polycyclic compounds to produce novel derivatives with marked antioxidant activities and as valuable intermediates for the pharmaceutical industry. Moreover, the compounds contained in the vehicles, due to their mechanism of action, can have a beneficial effect on the balance between oxidants and antioxidants in the body, minimizing the effects of oxidative stress. The results of this work may contribute to knowledge regarding vehicles with antioxidant potential. The use of vehicles for this type of research is therefore justified.